The pathophysiology of bronchial asthma involves reversible airway obstruction, mucus hypersecretion, an increase in vascular permeability, bronchial hyperreactivity, and airway inflammation. While infiltration of the lung with inflammatory cells such as neutrophils (PMNs), eosinophils, and mast cells has been observed in lavage fluid in both naturally occurring asthma and in human models of asthma, the role played by these cells in the lung in the pathogenesis of asthma is unknown. The overall goal of this proposal is to identify those aspects of the IgE-mediated inflammatory response that are modified in humans with atopic asthma. For example, it is not clear if this response is simply larger (an increased quantity of mediators released and cells recruited), if the response is more efficient (if the mediator release per cell is increased), or if the response is more effective (the end organ response to cells and mediators is increased). In order to test these hypotheses, atopic asthmatics and atopic nonasthmatic controls will undergo bronchoscopic antigen challenge into a localized portion of the lung with recruited inflammatory cells and mediators recovered at a later time by bronchoalveolar lavage (BAL). To test the hypothesis that the inflammatory response is larger, urinary leukotriene (LT) E4 levels immediately after challenge and total and differential cell counts in BAL fluid from the antigen challenged segment 24 hr after local antigen challenge will be quantitated. The hypothesis will also be tested that LTB4 is responsible for attracting PMNs after antigen challenge. To test the hypothesis that the inflammatory response is more efficient (cells recruited to the lungs of asthmatics are more "inflammatory" than those from nonasthmatics, i.e. they have been "primed" for an increase in mediator release), the in vitro release of mediators from neutrophils, eosinophils and macrophages recruited to the lung by local antigen challenge; a quantitative cytochemical analysis of granule content of neutrophils, eosinophils, and macrophages recovered by BAL; and the concentrations of neutrophil elastase, eosinophil products (major basic protein, cationic protein), and macrophage beta-glucuronidase in BAL fluid will be determined. The mechanism by which macrophages are primed for an increase in oxidant release will also be determined. To test the hypothesis that the inflammatory response is more effective in producing pathophysiologic changes in asthmatic than in nonasthmatic subjects, the airway inflammatory response and the influx of albumin into the airways will be determined. the hypothesis that eosinophils are primarily responsible for lung injury in this model will also be tested. These studies will provide important information concerning the function of inflammatory cells in the pathogenesis of allergic bronchial asthma. In addition, they will provide crucial information needed in order to develop novel strategies for the treatment of asthma using antiinflammatory agents.